Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data
- Institute for Global Health, University College London, United Kingdom
- MRC-University of Glasgow Centre for Virus Research, United Kingdom
- Sheffield Bioinformatics Core, The University of Sheffield, United Kingdom
- Sheffield Institute for Translational Neuroscience, The University of Sheffield, United Kingdom
- Sheffield Biomedical Research Centre, The University of Sheffield, United Kingdom
- Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom
- The Florey Institute for Host-Pathogen Interactions & Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, United Kingdom
- The Comprehensive Clinical Trials Unit at UCL , University College London, United Kingdom
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, United Kingdom
- Clinical Microbiology, NHS Greater Glasgow and Clyde, United Kingdom
- Research Computing, University College London, United Kingdom
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom
- Department of Infectious Diseases, Queen Elizabeth University Hospital, United Kingdom
- Division of Infection and Immunity, University College London, United Kingdom
Figures
Figure 1
Plots of posterior probability of healthcare-associated infection (HCAI) against prior probability of HCAI.
Plot of the posterior probability of healthcare-associated infection (HCAI) for (a) Glasgow and (b) Sheffield hospital onset COVID-19 infection cases from the sequence reporting tool algorithm against the prior probability of HCAI based only on time from admission to diagnosis, grouped by standard infection prevention and control classification recommended by Public Health England. Marginal histograms are displayed with bin-widths of 0.05.
Figure 2
Plot of the posterior probabilities of healthcare-associated infection (HCAI) estimated using the sequence reporting tool algorithm from a source on the current ward versus a source elsewhere in the hospital for (a) Glasgow and (b) Sheffield hospital onset COVID-19 infection cases grouped by standard Public Health England classification.
In cases where there are no close sequence matches in the dataset (including among community cases), the results returned are based solely on the priors and the metadata; this explains the fact that there are some cases with estimated posterior probability of infection on the ward greater than 0.5 for whom there were no sequence matches on the ward.
Figure 3
Maximum-likelihood phylogeny of the sequences found in Hospital 5 Unit 93 and Unit 92 up until the 16th of May of the Glasgow dataset.
The black lines represent the time from admission to sampling. The values below the line are the posterior probability for unit infection + the posterior probability of hospital infection from the sequence reporting tool. The tip nodes are coloured according to the local authority area of the community surveillance sequences (circles) or of the patients (crosses).
Figure 4
Maximum-likelihood phylogeny of the sequences found in location ‘0111’ in the Sheffield dataset, also including patients at several other ward locations.
The tree tip nodes are coloured according to ward locations. The black lines represent the time from admission to sampling. The values below the line are the posterior probability for unit infection + the posterior probability of hospital infection from the sequence reporting tool. The circle containing a number represents community sequences that are identical and at the base of this lineage (n = 36).
Appendix 1—figure 1
Proportion of cases sequenced in Greater Glasgow and Clyde Health Board between 1 March and 27 May (with sequence available as of 23 June 2020) by location of test (A).
Also displayed are the proportion of sequenced cases in the three focus hospitals subdivided by assessment and inpatient locations (B), and the proportion of hospital onset COVID-19 infection (HOCI) cases sequenced at these hospitals (C).
Appendix 1—figure 2
Home residence location of individuals in (a) the Glasgow dataset and (b) the Sheffield dataset, displayed by sample source (not including healthcare workers [HCWs]).
Locations are analysed using only the outer postcode, and as such random jitter (within longitude and latitude of 0.05) has been added to allow display without overlap of points. Plot created using ggmap for R with map obtained from Stamen maps. For Glasgow, 766 cases were included in the calibration set with estimates of τ = 0.15 and β = 0.0 for the geographic clustering model, whilst for Sheffield 446 cases were included in the calibration set with resulting estimates of τ = 0.84 and β = 0.16.
Appendix 1—figure 3
Frequency plot of all pairwise SNP differences among (a) all 1199 sequences in the Glasgow dataset and (b) all 1629 analysed sequences in the Sheffield dataset.
Appendix 1—figure 4
Maximum-likelihood tree for sequences found in Hospital 2 Unit 48 and Hospital 4 Unit 69 of the Glasgow dataset up until the 21st of April (inclusive).
The circles with numbers represent the number of community sequences that are identical and at the base of each lineage (n = 5, n = 35, n = 4). Tree tips with black circles represent further community sequences. The black lines represent the time from admission to sampling. The values below the line are the posterior probability for unit infection + the posterior probability of hospital infection from the sequence reporting tool.
Appendix 1—figure 5
Example of sequence reporting tool output with estimated very highly probable infection within unit.
Appendix 1—figure 6
Example of sequence reporting tool output with estimated probable infection within hospital.
Tables
Table 1
Summary of sequence reporting tool outputs for the Glasgow and Sheffield datasets, according to standard IPC definitions recommended by Public Health England regarding likelihood of HCAI.
| Glasgow data | Sheffield data | |||||
|---|---|---|---|---|---|---|
| IPC classification | IPC classification | |||||
| Indeterminate HCAI | Probable HCAI | Definite HCAI | Indeterminate HCAI | Probable HCAI | Definite HCAI | |
| n HOCI cases | 20 | 27 | 78 | 62 | 68 | 71 |
| Time from admission to sample*, days | 4.5 (3–6) | 11 (9-13) | 48 (26-83) | 5 (4–6) | 9 (8–13) | 22 (17–31) |
| Summary of sequence matches returned for each HOCI case | ||||||
| Close sequence match on ward | 5 (25.0) | 15 (55.6) | 53 (68.0) | 24 (38.7) | 46 (67.6) | 46 (64.8) |
| No close sequence match on ward, but match within hospital | 8 (40.0) | 7 (25.9) | 19 (24.4) | 34 (54.8) | 21 (30.9) | 21 (29.6) |
| No close sequence match anywhere within hospital | 7 (35.0) | 5 (18.5) | 6 (7.7) | 4 (6.5) | 1 (1.5) | 4 (5.6) |
| Close sequence match to one or more HCW | 1 (5.0) | 0 (0) | 13 (16.7) | 55 (88.7) | 61 (89.7) | 59 (83.1) |
| No close sequence match anywhere within dataset | 2 (10.0) | 1 (3.7) | 4 (5.1) | 4 (6.5) | 1 (1.5) | 4 (5.6) |
| Probability calculations | ||||||
| Prior probability of HCAI† | 0.39 (0.11–0.66) | 0.97 (0.92–0.99) | 1.00 (1.00–1.00) | 0.49 (0.29–0.66) | 0.92 (0.86–0.99) | 1.00 (1.00–1.00) |
| Posterior probability of HCAI‡ | 0.33 (0.02–0.67) | 0.98 (0.96–1.00) | 1.00 (1.00–1.00) | 0.40 (0.11–0.80) | 0.98 (0.93–1.00) | 1.00 (0.99–1.00) |
| Posterior probability of HCAI‡ category | ||||||
| Low (<30%) | 10 (50.0) | 4 (14.8) | 2 (2.6) | 25 (40.3) | 0 (0) | 0 (0) |
| Moderately low (≥30% and <50%) | 2 (10.0) | 0 (0) | 0 (0) | 12 (19.4) | 0 (0) | 0 (0) |
| Medium (≥50% and <70%) | 4 (20.0) | 0 (0) | 0 (0) | 4 (6.5) | 5 (7.4) | 3 (4.2) |
| High (≥70% and <85%) | 3 (15.0) | 0 (0) | 0 (0) | 8 (12.9) | 7 (10.3) | 2 (2.8) |
| Very high (≥85%) | 1 (5.0) | 23 (85.2) | 76 (97.4) | 13 (21.0) | 56 (82.4) | 66 (93.0) |
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Data shown as median (interquartile range) or n (%).
*Or first +ve test where known.
-
†Based on time from admission.
‡From source on ward or within hospital.
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HCAI: healthcare-associated infection; HOCI: hospital onset COVID-19 infection; HCW: healthcare worker; IPC: infection prevention and control.
Table 2
Summary of distinct outbreak events for the Glasgow and Sheffield datasets, according to standard PHE definition and with the addition of sequence data.
| Glasgow data | Sheffield data | |
|---|---|---|
| n HOCI cases | 125 | 201 |
| n ward locations | 44 | 38 |
| Sequence matches per HOCI case | ||
| n sequence matches from same ward, median (IQR, range) | 1 (0–5, 0–12) | 1 (0–4, 0–18) |
| n sequence matches from rest of hospital, median (IQR, range) | 3 (1–8, 0–52) | 27 (5–52, 0–150) |
| Standard PHE definition of outbreak event | ||
| HOCI cases part of ward outbreak event, n (%) | 95 (76.0) | 184 (91.5) |
| n ward outbreak events | 17 | 24 |
| n HOCI cases per ward outbreak event, median (IQR, range) | 4 (2–8, 2–17) | 5 (3.5–10.5, 2–28) |
| Days from first to last case in outbreak, median (IQR, range) | 8 (6–15, 0–31) | 18 (13–34, 3–68) |
| n wards with more than one distinct outbreak event | 0 | 0 |
| Outbreak events with sequence linkage | ||
| HOCI cases part of ward outbreak event, n (%) | 85 (68.0) | 140* (69.7) |
| n ward outbreak events | 16 | 33 |
| n HOCI cases per ward outbreak event, median (IQR, range) | 3.5 (2–8, 2–16) | 3 (2–4, 1–19) |
| Days from first to last case in outbreak, median (IQR, range) | 6 (4–9, 0–15) | 4 (2–8, 0–17) |
| n wards with more than one distinct outbreak event | 0 | 9† |
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* Includes two HOCIs which each showed a close sequence match to another case on the same ward with interval from admission to sample date ≤2 days.
†In three wards, there were three genetically distinct outbreak events.
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HOCI: hospital onset COVID-19 infection; IQR: interquartile range; PHE: Public Health England.
Additional files
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Supplementary file 1
Comma separated value file containing a list of the COG-UK identification codes for viral sequences included in the analysis.
- https://cdn.elifesciences.org/articles/65828/elife-65828-supp1-v2.zip
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Supplementary file 2
Details of the COVID-19 Genomics UK (COG-UK) consortium.
- https://cdn.elifesciences.org/articles/65828/elife-65828-supp2-v2.docx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/65828/elife-65828-transrepform-v2.docx
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Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data
eLife 10:e65828.
https://doi.org/10.7554/eLife.65828
